Ceftolozane-tazobactam, ceftazidime-avibactam and ceftazidime-avibactam plus aztreonam combination: Upcoming hope for hospital-acquired MDR/XDR Pseudomonas aeruginosa infections

Background: P. aeruginosa is a worrisome multidrug (MDR) or even extensively drug-resistant (XDR) nosocomial pathogen. Ceftolozane/tazobactam(C/T) and ceftazidime/avibactam (CAZ/AVI), novel combinations, were recently approved for the treatment of MDR Gram-negative pathogens. Objective: To assess the in vitro activity of C/T & CAZ/AVI and against MDR/XDR P. aeruginosa isolates , detect the synergistic activity of CAZ/AVI plus aztreonam (ATM) against metallo-β- lactamase )MβL( producers and to determine the virulence profile of the studied isolates. Methods: Eighty P. aeruginosa strains were isolated from hospitalized patients and screened for their antimicrobial susceptibility pattern by disk diffusion test. Different resistance mechanisms; beta-lactam hydrolyzing enzymes (ESβLs, AmpC, and class A & B carbapenemases), biofilm production and efflux pump-mediated colistin resistance mechanisms were characterized by the corresponding phenotypic methods. Multiplex PCR verified some resistance (blaVIM, blaKPC, mcr-1 & mcr-2) and virulence (exoU and exoS) genes. We applied E-test strip superposition method to detect synergistic effect between CAZ/AVI and ATM. Results: 32.5% and 52.5% of P. aeruginosa isolates were recovered as MDR and XDR isolates respectively. The frequency of beta-lactamase production reached 12.5% for ESβLs, 46.25% for AmpC, 21.4% for class A and 55.4% for class B carbapenemases. About 81.3% and 63.7% of the isolates proved susceptibility to CAZ/AVI and C/T respectively. While only 36.3% were ATM susceptible. Interestingly, combined use of CAZ/AVI with ATM completely restored susceptibility among MβL strains. Conclusion: Synergistic combination of CAZ/AVI with ATM could be promising therapy against MDR/XDR P. aeruginosa infections with MβL production.